Effect of inhibition of oxygen free radical on ovulation and progesterone production by the in-vitro perfused rabbit ovary

Miyazaki, Toshihisa; Sueoka, Kou; Dharmarajan, Arun; Atlas, Susan J.; Bulkley, Gregory B.; Wallach, Edward E.

doi:10.1530/jrf.0.0910207

Cited by 102 publications

(49 citation statements)

References 11 publications

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“…Furthermore, it was recently demonstrated that exposure to LH elevates ROS levels in ovarian follicles (39), and the suppression of ROS by superoxide dismutase in in vitro-perfused rabbit ovary preparations hinders ovulation (40). In this work we show that in vivo administration of broad-range scavengers of oxidative species such as BHA and NAC into the ovarian bursa of eCG/hCGtreated mice significantly reduces the rate of ovulation.…”

Section: Discussionsupporting

confidence: 49%

Reactive oxygen species are indispensable in ovulation

Shkolnik¹,

Tadmor²,

Ben‐Dor

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

300

213

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Ovulation is stimulated by the preovulatory surge of the pituitary luteinizing hormone (LH). Because the ovulatory response is commonly identified with inflammation, we explored the involvement of reactive oxygen species (ROS) in this process. Our experiments show that administration of broad-range scavengers of oxidative species into the ovarian bursa of mice, hormonally induced to ovulate, significantly reduced the rate of ovulation. LH-induced cumulus mucification/expansion, a necessary requirement for ovulation, was prevented by antioxidants both in vivo and in an ex vivo system of isolated intact ovarian follicles. Along this line, H 2 O 2 fully mimicked the effect of LH, bringing about an extensive mucification/expansion of the follicle-enclosed cumulusoocyte complexes. Impaired progesterone production was observed in isolated follicles incubated with LH in the presence of the antioxidant agents. Furthermore, LH-stimulated up-regulation of genes, the expression of which is crucial for ovulation, was substantially attenuated upon ROS ablation. This system was also used for demonstrating the role of ROS in phosphorylation and activation of the EGF receptor as well as its downstream effector, p42/44 MAPK. Together, our results provide evidence that ovarian production of ROS is an essential preovulatory signaling event, most probably transiently triggered by LH.ovary | cumulus expansion O vulation is an essential prelude for successful reproduction. The ovulatory process is initiated by the midcycle surge of the pituitary luteinizing hormone (LH) that induces substantial biochemical, molecular, and cellular changes, culminating in the release of a mature ovum surrounded by the cumulus cells (1). Before ovulation, the cumulus cells produce an extracellular, hyaluronan-rich matrix that brings about cumulus mucification and its expansion. This response to LH that is essential for ovulation (2) is subsequent to the expression of a set of specific genes (3) such as prostaglandin synthase 2 (Ptgs2) (4), hyaluronan synthase 2 (Has2) (5), tumor necrosis-stimulated gene 6 (Tnfaip6) (6), and CCAAT/enhancer-binding protein β (Cebpb), a downstream target of p42/44 MAPK (Erk1/2) (7). Also essential for ovulation is LH-induced progesterone receptor (Pgr) expression as well as progesterone production (8).Numerous genes related to inflammation are induced in preovulatory follicles by the LH surge (9-12). Moreover, ovulation is suppressed by agents that inhibit acute inflammatory reactions (13). The analogy of ovulation with an acute inflammation (9, 14) may suggest a role for reactive oxygen species (ROS) along this process. ROS originate from inflammatory cells, such as macrophages and neutrophils, which are massively recruited after the LH surge to the ovary (15), and their depletion impairs ovulation (16, 17). Cyclooxygenase 2 (Ptgs2), the expression of which is a hallmark for LHinduced ovulation, is associated with inflammation and generates ROS (18). ROS are also byproducts of monooxygenase reactions mediated by the P450...

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Section: Discussionsupporting

confidence: 49%

Reactive oxygen species are indispensable in ovulation

Shkolnik¹,

Tadmor²,

Ben‐Dor

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

300

213

View full text Add to dashboard Cite

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“…Reactive oxygen species may be released in connection with follicle rupture, because inhibition of oxygen free radicals leads to inhibition of ovulation (17). Reactive oxygen species are thought to play a role in oocyte maturation (18).…”

Section: Follicular Glutathione S-transferasementioning

confidence: 99%

Glutathione S-transferases in human ovarian follicular fluid

Bisseling¹,

Knapen²,

Goverde³

et al. 1997

Fertility and Sterility

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“…Furthermore, subcutaneous administration of a large dose (30 mg/kg) of native SOD but not H,O,-inactivated SOD also inhibited the ovulation by 40-50%. Recent study also revealed that SOD inhibited hCG-induced ovulation in an isolated perfused ovary of the rabbit [29]. Thus, the inhibition of hCG-induced ovulation by SM-SOD might principally be due to dismutation of superoxide radicals rather than nonspecific toxicity of the SM moiety.…”

Section: Discussionmentioning

confidence: 98%

Dynamic aspects of ovarian superoxide dismutase isozymes during the ovulatory process in the rat

Sato¹,

Kobuchi

Edashige³

et al. 1992

FEBS Letters

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To investigate the role of superoxide dismutasc (SOD) in the ovulatory process, SOD isoymes and their mRNAs were determined in the ovary of 22-day-old rat. After treatment with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG), ovarian sctivity of Mn-SOD decreased markedly while Cu/Zn-SOD remained unchanged. However, the ovarian level of mRNA for Mn-SOD markedly increased after hCG-treatment while that for Cu/Zn-SOD decreased only slightly. Ovulation WPS inhibited by intravenous injection of a long-acting SOD, These results suggested that superoxide radicals in the ovary might play a critical role in the mechanism for hCG-induced ovulation.

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Effect of inhibition of oxygen free radical on ovulation and progesterone production by the in-vitro perfused rabbit ovary

Cited by 102 publications

References 11 publications

Reactive oxygen species are indispensable in ovulation

Reactive oxygen species are indispensable in ovulation

Glutathione S-transferases in human ovarian follicular fluid

Dynamic aspects of ovarian superoxide dismutase isozymes during the ovulatory process in the rat

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